Browsing by Subject "Parkinson's disease"

Now showing 1 - 16 of 16
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    Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease
    (Murcia : F. Hernández, 1997) Anglade, P.; Vyas, S.; Javoy-Agid, F.; Michel, P.P.; Marquez, J.; Mouatt-Prigent, A.; Ruberg, M.; Hirsch, E.C.; Agid, Y.; Herrero Ezquerro, María Trinidad
    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss confined mostly to dopaminergic neurons of the substantia nigra. Several factors, including oxidative stress, and decreased activity of complex 1 mitochondrial respiratory chain, are involved in the degenerative process. Yet, the underlying mechanisms leading to dopaminergic cell loss remain elusive. Morphological assessrnent for different modes of cell death: apoptosis, necrosis or autophagic degeneration, can contribute significantly to the understanding of this neurona1 loss. Ultrastructural examination revealed characteristics of apoptosis and autophagic degeneration in melanized neurons of the substantia nigra in PD patients. The results suggest that even at the final stage of the disease, the dopaminergic neurons are undergoing active process of cell death.
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    Calidad de vida y autocuidado en enfermos de Parkinson de un hospital comarcal: estudio descriptivo
    (Murcia: Servicio de Publicaciones de la Universidad de Murcia, 2019) Llagostera Reverter, Irene; López Alemany, Mario; Sanz Forner, Rosana; González Chordá, Víctor M.; Orts Cortés, Mª Isabel
    Objetivos:Determinar el grado de autocuidadoy la calidad de vida en una muestra de pacientes con Enfermedad de Parkinson en estadios inicialesy conocer las dimensiones de autocuidado y calidad de vida más afectadas. Estudiar la relación entre los síntomas no motores con estas medidas de resultado.Metodología:Estudio observacional transversal realizado en una muestra de 21 enfermos de Parkinson grado I, II de la escala Hoenh Yarh. Se estudió el nivel de autocuidados, calidad de vida, síntomas no motores y nivel de salud percibido. Se realizó análisis descriptivo, inferencial y de correlación con el paquete estadístico SPSS v.20.Resultados:La edad media de la muestra fue de 71,86 (dt8,93) años, el 52,4% eran hombres. El nivel medio de autocuidados fue de 1,14 (dt0,35) siendo la dimensión más afectada el uso de medicamentos con una autonomía completa del 61,9% y 17,28 (dt7,75) para la calidad de vida siendo la dimensión más afectada el disconfort corporal (m=35,03; dt19,61). Se observó correlación baja entrelos síntomas no motores y la calidad de vida (r=0,246;p=0,022), pero no entre los síntomas no motores y el autocuidado (r=0,010;p=0,662).Conclusiones:El nivel de autocuidados y calidad de vida de la muestra estudiada es adecuado. Las dimensiones de calidad de vida más afectadas son el disconfort corporal seguida por el deterioro cognitivo y los síntomas no motores están relacionados con el nivel de calidad de vida. Es relevante considerar estos aspectos en el desarrollo de intervenciones de educación terapéutica dirigidas a pacientes con Parkinson.
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    Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence
    (MDPI, 2021-12) Herrero Ezquerro, María Trinidad; Laorden Carrasco, María Luisa; Cuenca Bermejo, Lorena; Almela Rojo, Pilar; Navarro Zaragoza, Javier; González Cuello, Ana María; Fernández Villalba, Emiliano; Enfermería
    Dysautonomia is a common non-motor symptom in Parkinson’s disease (PD). Most dysautonomic symptoms appear due to alterations in the peripheral nerves of the autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. The degeneration of sympathetic nerve fibers and neurons leads to cardiovascular dysfunction, which is highly prevalent in PD patients. Cardiac alterations such as orthostatic hypotension, heart rate variability, modifications in cardiogram parameters and baroreflex dysfunction can appear in both the early and late stages of PD, worsening as the disease progresses. In PD patients it is generally found that parasympathetic activity is decreased, while sympathetic activity is increased. This situation gives rise to an imbalance of both tonicities which might, in turn, promote a higher risk of cardiac damage through tachycardia and vasoconstriction. Cardiovascular abnormalities can also appear as a side effect of PD treatment: L-DOPA can decrease blood pressure and aggravate orthostatic hypotension as a result of a negative inotropic effect on the heart. This unwanted side effect limits the therapeutic use of L-DOPA in geriatric patients with PD and can contribute to the number of hospital admissions. Therefore, it is essential to define the cardiac features related to PD for the monitorization of the heart condition in parkinsonian individuals. This information can allow the application of intervention strategies to improve the course of the disease and the proposition of new alternatives for its treatment to eliminate or reverse the motor and non-motor symptoms, especially in geriatric patients.
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    Effectiveness of the botulinum toxin for treating sialorrhea in patients with Parkinson’s disease: a systematic review
    (MDPI, 2019-03-06) Ruiz Roca, Juan Antonio; Pons-Fuster López, Eduardo; López Jornet, María Pía; Dermatología, Estomatología, Radiología y Medicina Física; Facultades de la UMU::Facultad de Medicina
    The main objective was to assess the efficacy of botulinum toxin-based treatment for sialorrhea in adult patients with Parkinson’s disease. The search was performed by using the Medline-PubMed, EMBASE and Cochrane Library databases from January 2000–December 2017, in English/Spanish in patients with Parkinson’s disease and sialorrhea. The methodological quality of trials was carried out by following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and the Newcastle–Ottawa Scale (NOS). Finally, a total of 21 articles were identified as fulfilling the inclusion criteria. There is no consensus regarding the site of injection of the toxin (single or multiple points), toxin dose or follow-up period. In all cases there was a reduction of sialorrhea. Treatment safety increases with the use of ultrasonography. Effects approximately occur at one week post-injection and for 3–5 months. Botulinum toxin is an effective therapeutic strategy or option in treating sialorrhea in adult patients with Parkinson’s disease. More studies with a better design, larger samples and a longer follow-up period are required to confirm these data.
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    Gene therapy for Parkinson's disease: recent achievements and remaining challenges
    (Murcia : F. Hernández, 2001) Castro, M.G.; David, A.; Hurtado-Lorenzo, A.; Suwelack, D.; Millan, E.; Verakis, T.; Xiong, W.D.; Yuan, X.P.; Lowenstein, P.R.
    Gene therapy is the use of nucleic acids as drugs. Thus, ways had to be developed to deliver this new generation of drugs to target tissues. Various viral and non-viral vectors have been engineered to carry potentially therapeutic nucleic acids into diseased organs or target cells. The brain offers a particular challenge for gene delivery to its constituent cells: it is encased by the skull, separated from the general circulation by the blood brain barrier, and made up of mostly non-dividing cells. The skull limits direct injection of vectors into the brain, the blood brain barrier inhibits the easy entry of vectors injected into the bloodstream, and post mitotic target cells restrict what type of vector can be used to deliver genes to the brain. We will discuss the main challenges faced by gene delivery to the brain, i.e. immune responses to the delivery vectors and therapeutic transgenes and length of duration of the therapy specifically as applied to Parkinson's disease. We will also discuss therapeutic strategies, which could be implemented to treat Parkinson's disease, and the models in which they have been tested.
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    Gentiopicroside alleviates neuroinflammation in Parkinson's disease by mediating microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway
    (Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Shen Hong; Song Hui; Sun Qiang; Biología Celular e Histología
    Objective. The study aimed to evaluate the therapeutic potential of gentiopicroside (GPS) in Parkinson's disease (PD) through both in vitro and in vivo experiments, focusing on elucidating the underlying mechanisms of its action. Methods. To achieve this, a PD model was established in C57BL6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by assessment of behavioral changes, pathological alterations, microglial activation, and neuro-inflammation. Simultaneously, a cellular PD model was developed in the BV-2 mouse microglia cell line by exposing them to 1-methyl-4-phenyl-pyridinium (MPP+). The expression of pro-inflammatory molecules was quantified using enzyme-linked immunosorbent assay (ELISA), while pyroptosis was analyzed by flow cytometry with caspase-1/PI double staining. The expression of key factors in the nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway was determined by immunoblotting. Results. The findings revealed that GPS effectively mitigated motor deficits, neurological impairments, microglial activation, and neuroinflammation in the MPTP-induced mouse model of PD. Additionally, GPS protected BV-2 cells from MPP+-induced inflammatory cytokine production and pyroptosis. Mechanistic studies indicated that GPS may exert its neuroprotective effects by inactivating the NF-κB/NLRP3/GSDMD-mediated pyroptotic pathway in both in vivo and in vitro settings. Conclusion. GPS exhibits neuroprotective effects in PD by suppressing microglia-mediated neuro-inflammation and pyroptosis, suggesting its potential as a favorable therapeutic agent for PD treatment
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    In situ architecture of neuronal α-Synuclein inclusions
    (Nature Research, ) Trinkaus, Victoria A.; Riera-Tur, Irene; Bauerlein, Felix J.B.; Guo, Qiang; Arzberger, Thomas; Baumeister, Wolfgang; Dudanova, Irina; Hipp, Mark S.; Ulrich Hartl, F.; Fernández-Busnadiego, Rubén; Martínez Sánchez, Antonio; Ingeniería de la Información y las Comunicaciones
    The molecular architecture of α-Synuclein (α-Syn) inclusions, pathognomonic of various neurodegenerative disorders, remains unclear. α-Syn inclusions were long thought to consist mainly of α-Syn fibrils, but recent reports pointed to intracellular membranes as the major inclusion component. Here, we use cryo-electron tomography (cryo-ET) to image neuronal α-Syn inclusions in situ at molecular resolution. We show that inclusions seeded by α-Syn aggregates produced recombinantly or purified from patient brain consist of α-Syn fibrils crisscrossing a variety of cellular organelles. Using gold-labeled seeds, we find that aggregate seeding is predominantly mediated by small α-Syn fibrils, from which cytoplasmic fibrils grow unidirectionally. Detailed analysis of membrane interactions revealed that α-Syn fibrils do not contact membranes directly, and that α-Syn does not drive membrane clustering. Altogether, we conclusively demonstrate that neuronal α-Syn inclusions consist of α-Syn fibrils intermixed with membranous organelles, and illuminate the mechanism of aggregate seeding and cellular interaction.
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    Induction system of neural and muscle lineage cells from bone marrow stromal cells; a new strategy for tissue reconstruction in degenerative diseases
    (Murcia : F. Hernández, 2009) Kitada, Masaaki; Dezawa, Mari
    Since bone marrow stromal cells (MSCs) are easily accessible both from healthy donors and patients, and can be expanded on a therapeutic scale, they have attracted attention for cell-based therapy. MSCs contribute to the protection of host tissue after transplantation by Immune modulation and trophic effect. They also have an ability to differentiate into other cell kinds that will replenish lost cells in the degenerated tissue. This review discusses the potential of MSCs for tissue reconstruction in neuro- and muscledegenerative diseases and their differentiation capacity into functional cells.
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    Inflammation and infection in Parkinson`s disease
    (Murcia : F. Hernández, 2006) Arai, H.; Furuya, T.; Mizuno, Y.; Mochizuki, H.
    The hallmark of Parkinson’s disease (PD) is a specific degeneration of dopaminergic neurons in the substantia nigra (SN). The cause of nigral dopaminergic neuronal cell death in PD and its underlying mechanisms remain elusive, however, involvement of inflammatory events has been postulated because inflammatory features have been described in the brain of PD patients. Some evidence also suggest that a possible deleterious effects of neuroinflammatory processes by infection in experimental models of neurodegenerative disease. In this review, we summarize and discuss the latest findings regarding inflammation in PD. Especially, we focused on the relationship between infection and PD.
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    Investigación en enfermedades neurodegenerativas. Evitando la epidemia "silenciosa" del siglo XXI.
    (Murcia : Servicio de Publicaciones de la Universidad de Murcia, 2008) Herrero Ezquerro, María Trinidad; Departamentos y Servicios::Departamentos de la UMU::Anatomía Humana y Psicobiología
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    Mechanism of the protective effect of 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside on MPTP-induced Parkinson's disease mice
    (2026) Xiaolin Dong; Qingyun Li; Yanping Li; Furong Jin; Jingting Lu; Chengda Han; Lianbing Lin; Gang Wu1; Biología Celular e Histología
    Background and purpose. Parkinson's disease (PD) is a common neurodegenerative disorder with a complex pathogenesis. 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) is one of the main active components of Polygonum multiflorum Thunb., which has therapeutic effects in various neurodegenerative diseases. The aim of this study was to explore the influence of TSG on the PD process. Methods. The PD mouse model was constructed via the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD process was evaluated via behavioral tests, HE staining, immunohistochemistry, and immunofluorescence. The levels of related proteins and inflammatory factors were detected via western blotting and ELISA. The effect of TSG on the intestinal flora of MPTP-induced PD mice was evaluated through 16S rDNA sequencing. Results. TSG intervention can significantly alleviate motor dysfunction in PD mice, increase the number of TH-positive neurons in the substantia nigra, inhibit the accumulation of α-syn and glial cell activation, reduce the expression of the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and COX2 proteins in the substantia nigra and colon, inhibit neuroinflamma-tion and intestinal inflammation, decrease the levels of LPS, LBP, TNF-α, IL-1β, and IL-6 in the serum, suppress systemic inflammation, reduce damage to the blood-brain barrier (BBB) and intestinal barrier in PD mice, and restore species diversity and abundance of the intestinal flora in PD mice to a certain extent. Conclusion. TSG can improve motor coordination ability, systemic and neuroinflammatory levels, BBB injury, intestinal barrier injury, and the intestinal flora composition of PD mice, suggesting that TSG has a protective effect on MPTP-induced PD mice.
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    MiRNAs participate in the diagnosis, pathogenesis and therapy of Parkinson's disease
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lu, Xuexin; Cui, Zhijie; Liu, Shuang; Yin, Feng
    MicroRNAs (miRNAs), one kind of posttranscriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes, including Parkinson’s disease. At present, the pathogenesis of Parkinson's disease is not clear, although many studies suggest that miRNAs play a very important role in the progress of Parkinsonism. This paper reviews the biological characteristics of miRNAs and summarizes the progress of miRNAs in reference to the diagnosis and pathogenesis of Parkinson’s disease. It even considers miRNAs as a potential target for Parkinson’s disease therapy
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    Pathological changes in dendrites of substantia nigra neurons in Parkinson's disease: a Golgi study
    (Murcia : F. Hernández, 1991) Patt, Stephan; Gertz, Hermann-Josef; Gerhard, Lieselotte; Cervós-Navarro, J.
    Neurons of the substantia nigra show severe morphological changes in Parkinson's disease. Pathological alterations of cell bodies have been described, whereas those of neuronal processes have hardly been investigated. Golgi impregnation has been the chosen method for demonstrating neuronal processes and dendritic and somatic spines. We therefore used the Golgi-Braitenberg method to qualitatively and semi-quantitatively study the substantia nigra of eight patients with Parkinson's disease compared with eight control cases. Golgi impregnation of substantia nigra neurons was good in al1 control cases. In full agreement with the analysis of Braak and Braak (1986) three neuronal types within the substantia nigra were found. In cases of Parkinson's disease, severe pathological changes such as decrease of dendritic length, loss of dendritic spines and severa1 types of dendritic varicosities were found only in the melanin-containing pars compacta neurons. Pars reticulata nerve cells were intact. These findings support the predominant role played by the dopaminergic efferent pathway in the degenerative process. The afferent pathway was not affected. This suggests that the substantia nigra lesion is primary in Parkinson's disease. Loss of neurons found in H & E sections corresponded to a lesser amount of impregnated pars compacta neurons in cases with Parkinson's disease when compared to controls. Evidences exist that the duration of the disease may be related to the extent of pathologically altered Golgi-impregnated pars compacta cells. The amount of Lewy bodies in H & E sections corresponded to the quantity of round varicosities in impregnated pars compacta neurons. These round dendritic varicosities were considered to be Lewy body inclusions. They seem to have no influence on the dendritic spine density and morphology in most cases.
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    Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease
    (Oxford Univeristy Press, 2021-03-11) Thomas, George E.C.; Zarkali, Angeliki; Ryten, Mina; Shmueli, Karin; Gil Martínez, Ana Luisa; Leyland, Louis-Ann; McColgan, Peter; Acosta-Cabronero, Julio; Lees, Andrew J.; Weil, Rimona S.; Ingeniería de la Información y las Comunicaciones
    The mechanisms responsible for the selective vulnerability of specific neuronal populations in Parkinson’s disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions of 96 patients with Parkinson’s disease and 35 control subjects using quantitative susceptibility mapping. We estimated the expression of 15 745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson’s disease relative to controls. Applying gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile and identified the sets of genes with spatial expression profiles in control brains that correlated significantly with the spatial pattern of cortical iron deposition in Parkinson’s disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. Furthermore, we demonstrated that the genes differentially expressed in Parkinson’s disease are associated with the pattern of cortical expression identified in this study. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson’s disease, particularly the processes involving iron accumulation.
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    The Golgi complex of dopaminergic enteric neurons is fragmented in a hemiparkinsonian rat model
    (Wiley, 2023-10-19) Mireia Cara-Esteban; María Pilar Marín; Martínez Alonso, Emma; Sergio Martínez-Bellver; Vicent Teruel-Martí; Martínez Menárguez, José Ángel; Mónica Tomás; Biología Celular e Histología; Facultad de Medicina
    Since gastrointestinal disorders are early consequences of Parkinson's disease (PD), this disease is clearly not restricted to the central nervous system (CNS), but also significantly affects the enteric nervous system (ENS). Large aggregates of the protein α-synuclein forming Lewy bodies, the prototypical cytopathological marker of this disease, have been observed in enteric nervous plexuses. However, their value in early prognosis is controversial. The Golgi complex (GC) of nigral neurons appears fragmented in Parkinson's disease, a characteristic common in most neurodegenerative diseases. In addition, the distribution and levels of regulatory proteins such as Rabs and SNAREs are altered, suggesting that PD is a membrane traffic-related pathology. Whether the GC of enteric dopaminergic neurons is affected by the disease has not yet been analyzed. In the present study, dopaminergic neurons in colon nervous plexuses behave as nigral neurons in a hemiparkinsonian rat model based on the injection of the toxin 6-OHDA. Their GCs are fragmented, and some regulatory proteins' distribution and expression levels are altered. The putative mechanisms of the transmission of the neurotoxin to the ENS are discussed. Our results support the possibility that GC structure and the level of some proteins, especially syntaxin 5, could be helpful as early indicators of the disease. Research Highlights: The Golgi complexes of enteric dopaminergic neurons appear fragmented in a Parkinson's disease rat model. Our results support the hypothesis that the Golgi complex structure and levels of Rab1 and syntaxin 5 could be helpful as early indicators of the disease.
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    The synergetic effect of edaravone and scutellarin in the MPP(+)-induced cell model of Parkinson's disease
    (Universidad de Murcia, Departamento Histología e Histopatología, 2025) Wei Wei; Wu Jing; Zhang Dandan; Xu Shoucheng; Wang Yi; Li Xuezhong; Yu Ming; Chen Xiaopeng; Biología Celular e Histología
    Parkinson's disease (PD) is a limb movement disorder caused by the degeneration of brain neurons and seriously affects the quality of life of the elderly. However, the current drugs are symptomatic treatments that cannot prevent or delay the development of the disease. Targeted therapy for pathogenesis may be the direction of development in the future. Oxidative stress and the inflammatory response are involved in the pathogenesis of PD. Edaravone and scutellarin have been studied in antioxidant and anti-inflammatory reactions. The focus of this study is whether there is synergy between the two and its mechanism. Through research, we found that edaravone and scutellarin at different dose combinations have synergistic effects in 1-methyl-4-phenylpyridinium (MPP+)-induced PC12 cells using the Chou-Talalay joint index method. According to the CompuSyn software calculation, the results showed that the combination index (CI) of the combined application of 15 μM edaravone and 15 μM scutellarin was the lowest, indicating that the synergistic effect was the best. Compared with the single drug, the synergy increased superoxide dismutase (SOD) and reduced glutathione (GSH) levels, reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and enhanced the anti-apoptosis ability in the MPP(+) induced cell model of PD.